Telomerase activity and in situ telomerase RNA expression in malignant and non-malignant lymph nodes.

AIMS/BACKGROUND: Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours, but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to determine whether telomerase expression is useful for the detection of occult malignant cells in lymph nodes. METHODS: Telomerase activity was compared with histological findings in 123 surgically removed lymph nodes submitted for routine or frozen section diagnosis. Telomerase activity was measured using a modified, semi-quantitative PCR-based telomeric repeat amplification protocol (TRAP). The assay was adapted for single 5 microns OCT embedded cryostat sections. In either fresh tissues or cryostat sections, normalised activity was linear when compared with protein concentration. Furthermore, using an in situ hybridisation method, the human telomerase RNA (hTR) component was measured in a subset of negative and positive nodes. RESULTS: Most (96%) of the 97 histologically negative nodes expressed low levels of activity (mean value of positive samples = 3.0 units/microgram protein) which may be derived from activated lymphocytes that express telomerase activity. All 26 malignant nodes (17 metastases, nine lymphomas) expressed telomerase (mean value = 17.8 units/microgram protein). The rank order levels between the two groups differed significantly (p = 0.0002). In situ results showed clearly that the hTR was expressed relatively highly in metastatic cancer cells and at lower levels in germinal centres of secondary follicles. CONCLUSIONS: Although expression of telomerase by activated lymphocytes may limit its usefulness, measurement of enzyme activity combined with detection of hTR using in situ hybridisation may assist in the histopathological diagnosis of lymph nodes.     

Hydrocelectomy under local anaesthesia in a Nigerian adult population

Background

Hydrocele is abnormal collection of serous fluid in the tunica vaginalis or a patent processus vaginalis. It is commonly encountered in our practice and often requires surgical treatment. However in our setting and in many underdeveloped countries, availability of general anaesthetic service is poor due to lack of trained personnel and equipment.

Objectives

To ascertain the practicability and acceptability of hydrocelectomy under sedation and local anaesthesia in Nigerian adults with hydrocele

Patients and Methods

A prospective study was carried out over a two year period on patients that had hydrocelectomy at the surgery unit of the Obafemi Awolowo University Teaching Hospitals Complex, Wesley Guild Hospital, Ilesa. Consecutive patients with diagnosis of hydrocele who consented had hydrocelectomy using intramuscular diazepam sedation and spermatic-cord block with 0.5% plane xylocaine and the scrotum infiltrated with same along the line of incision.

Results

Fifty adult patients were studied: age range 15–94 years. Eighty percent of the patients had unilateral hydrocele and the commonest type was vaginal hydrocele (94%). All patients had hydrocelectomy, 96% were under local anaesthesia while 4% were converted to general anaesthesia. All patients except one prefer to have future surgery under such local anaesthesia and sedation.

Conclusion

Hydrocelectomy under local anaesthesia and sedation is practicable and was tolerated and accepted by the adults patients studied.     

Biosynthetic growth hormone therapy in children with growth hormone deficiency: Experience at AIIMS,New Delhi

A total of 20 previously untreated children with growth hormone deficiency (GHD) were treated for one year with biosynthetic human growth hormone (hGH). The mean chronologic age was 9.43±3.52 years with a height age of 5.02 years, and bone age 9.43±3.52 (TW2-RUS) 6.42 years. The mean pretreatment growth velocity was 2.43±0.90 cm/year. Of these 14 children had complete GHD (peak GH levels less than 5 ng/ml) and 6 had partial GHD. They were treated with recombinant GH in a dose of 0.5 IU/kg/week divided into 6–7 injections per week subcutaneously at night. The mean growth velocity increased to 8.88±2.10 cm/yr at the end of 6 months and 8.00±2.21 cm/yr at 12 months. The actual gain ranged from 6–11 cm in a year. There were no local adverse reactions. One child developed vitiligo of the face and another transient hyperglycemia.     

Pilot study of oral rapamycin to prevent restenosis in patients undergoing coronary stent therapy: Argentina Single-Center Study (ORAR Trial)

Rapamycin-coated stents are associated with low restenosis rates, but the ability of oral rapamycin to prevent restenosis is unknown. From December 2001 through February 2002, thirty-four patients with 49 lesions were treated with oral rapamycin for 1 month following percutaneous coronary intervention (PCI) with bare stents. Patients received a loading dose of 6 mg rapamycin followed by a daily dose of 2 mg. Rapamycin blood levels were measured in all patients during the third week of treatment. Cholesterol and triglycerides were evaluated before and 1 month after treatment. A 6-month follow-up angiogram was performed in all patients. Angiographic binary restenosis (> 50%), target lesion revascularization (TLR), late loss, treatment compliance and major adverse cardiac events were analyzed independent of rapamycin levels. Baseline characteristics included a history of diabetes in 35% of patients and the presence of in-stent restenosis in 24.5% of lesions (12/49). The rapamycin was well tolerated and only 1 patient discontinued the therapy due to mild side effects. Angiographic restenosis and TLR at 6 months was present in 26.5% of lesions (13/49). Restenosis in de novo lesions was 18.9% (7/37) compared to 50% of in-stent restenotic lesions (6/12; p = 0.08). Restenosis in de novo lesions in patients with rapamycin levels > 8 ng/ml was 0% (0/12), whereas it was 24% (6/25) when the rapamycin levels were < 8 ng/ml (p = 0.07). Late loss was significantly lower when rapamycin levels were > 8 ng/ml (0.3 mm versus 0.9 mm, respectively; p = 0.04). Thus, in this observational study, oral rapamycin administered for 1 month after PCI with bare stenting was safe and well tolerated. Higher therapeutic rapamycin blood levels were associated with a lower late loss and a trend toward a lower restenosis rate in de novo lesions.     

Histopathologic Alterations after Endovascular Radiation and Antiproliferative Stents: Similarities and Differences

BACKGROUND: Endovascular radiation and drug-eluting antiproliferative stents in experimental animals (normal pigs and rabbit arteries) show a decrease in the neointimal growth at 1 month vs. controls. However, this is accompanied by delayed healing characterized by persistence of neointimal fibrin (with or without inflammation), a decrease in smooth muscle cells, and incomplete endothelialization. Conversely, stainless steel control stents show complete healing with the neointima consisting of smooth muscle cells in a proteoglycan-collagen matrix and near complete luminal surface endothelialization. RESULTS: Long-term (3 and 6 months) animal studies fail to show any benefit with radiation or drug-eluting stents. These experimental results are discrepant from those seen clinically in man where both therapies have shown benefit at 6 months, suggesting that animal data may not be predictive of clinical results. The main differences can be explained on the basis of preclinical studies performed in juvenile animals without underlying atherosclerosis, which leads to accelerated healing in animals vs. man such that 1 month animal data likely correspond to 6 months in man. Therefore long-term (24-30 months) angiographic and/or IVUS follow-up studies in man will be required to determine if drug-eluting stents will behave similarly to animal studies at 3 and 6 months.     

Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features.

PURPOSE: We investigated the aberrant methylation profile of prostate cancers and correlated the data with clinical findings. EXPERIMENTAL DESIGN: Gene promoter methylation was analyzed in 101 prostate cancer samples. In addition, we analyzed 32 nonmalignant prostate tissue samples, which included 25 with benign disease, benign prostatic hypertrophy, or prostatitis, and 7 normal tissues adjacent to cancer. The methylation status of 10 genes was determined. The methylation index (MI) was calculated as a reflection of the methylated fraction of the genes examined. RESULTS: Methylation percentages of the genes tested in prostate cancers were: RARbeta, 53%; RASSF1A, 53%; GSTP1, 36%; CDH13, 31%; APC, 27%; CDH1, 27%; FHIT, 15%; p16(INK4A), 3%; DAPK, 1%; and MGMT, 0%. Methylation percentages in nonmalignant tissues were much lower. For clinicopathological correlations, we divided the cancer cases into low (6 or less) or high (7 or more) Gleason score (GS) groups, and into low (8 ng/ml or less) or high (greater than 8 ng/ml) preoperative serum prostate-specific antigen (PSA) groups. Methylation of RASSF1A, GSTP1, RARbeta, and CDH13 genes was significantly more frequent in the high GS group than in the low GS group. Methylation of RASSF1A, CDH1, and GSTP1 genes was significantly more frequent in the high PSA group than in the low PSA group. The median MIs were significantly higher in the high GS and the high PSA groups. According to the Spearman rank-correlation test, there was significant correlation between MI and GS (coefficient = 0.43, P < 0.0001) and the preoperative serum PSA (coefficient = 0.37, P = 0.0003). CONCLUSIONS: Our results indicate that the methylation profile of prostate cancers correlates with clinicopathological features of poor prognosis.